NM_001173467.3:c.1161C>T

Variant names:

• chr12-53328281-G-A
• rs1316822708
• NM_001173467.3:c.1161C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001173467.3(SP7):​c.1161C>T​(p.Gly387Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SP7 NM_001173467.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.599
• Publications: 0 publications found

Genes affected

SP7 (HGNC:17321): (Sp7 transcription factor) This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein is a bone specific transcription factor and is required for osteoblast differentiation and bone formation.[provided by RefSeq, Jul 2010]

SP7 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 12

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 12-53328281-G-A is Benign according to our data. Variant chr12-53328281-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3678261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.599 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001173467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP7	NM_001173467.3	MANE Select	c.1161C>T	p.Gly387Gly	synonymous	Exon 3 of 3	NP_001166938.1	Q8TDD2-1
	SP7	NM_152860.2		c.1161C>T	p.Gly387Gly	synonymous	Exon 2 of 2	NP_690599.1	Q8TDD2-1
	SP7	NM_001300837.2		c.1107C>T	p.Gly369Gly	synonymous	Exon 3 of 3	NP_001287766.1	Q8TDD2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP7	ENST00000536324.4	TSL:2 MANE Select	c.1161C>T	p.Gly387Gly	synonymous	Exon 3 of 3	ENSP00000443827.2	Q8TDD2-1
	SP7	ENST00000303846.3	TSL:1	c.1161C>T	p.Gly387Gly	synonymous	Exon 2 of 2	ENSP00000302812.3	Q8TDD2-1
	SP7	ENST00000537210.2	TSL:1	c.1107C>T	p.Gly369Gly	synonymous	Exon 2 of 2	ENSP00000441367.2	Q8TDD2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458854 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725576

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110390

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.5
DANN	Benign	0.89
PhyloP100		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1316822708; hg19: chr12-53722065;